Activity regulated cytoskeletal
protein (
Arc), c-fos and zif268 are immediate early genes (IEGs) important for adult brain plasticity. We examined developmental expression of these IEGs and the effect of neonatal noradrenergic lesion on their expression in developing and mature brain.
N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), a specific noradrenergic
neurotoxin, was administered to rats on postnatal day (PND) 3 and in situ hybridization was used to assay
Arc, c-fos and zif268
mRNA on PND 13, 25 and 60. In contrast to decreases in
Arc, c-fos and zif268 expression produced by noradrenergic lesions of mature brain, lesions on PND 3 yield a strikingly different effect. Neonatal lesions produce increases in c-fos and zif268 expression in specific frontal cortical layers on PND 13, while
Arc shows no change. These lesions lead to increases in zif268 expression in frontal cortical layers on PND 25, with no changes in c-fos or
Arc expression, and on PND 60 they produce a significant increase in c-fos expression in hippocampus with no significant changes in
Arc or zif268 expression. 2-[2-(2-Methoxy-1,4-benzodioxanyl)]
imidazoline hydrochloride (
RX821002), an
alpha-2 adrenergic receptor (A2AR) antagonist, administered to control PND 60 animals produces elevations of
Arc, zif268 and c-fos mRNAs. This response was eliminated in animals lesioned with
DSP-4 on PND 3. These data indicate that
norepinephrine regulation of IEG expression differs in developing and mature brain and that loss of developmental
norepinephrine leads to abnormally high postnatal IEG expression. Previous studies have shown an important role for
norepinephrine in brain development. Our data support the idea that
norepinephrine plays an important role during CNS development and that changes in noradrenergic signaling during development may have long lasting effects, potentially on learning and memory.